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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 336 (1987), S. 262-266 
    ISSN: 1432-1912
    Keywords: Conditioning ; Apomorphine ; Dopamine receptors ; Stereotyped behaviour ; Akinesia ; Ptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Apomorphine, in an intermediate dose (0.18 mg/ kg s.c.) decreased dopamine turnover and produced signs generally attributed to a decrease in dopaminergic neurotransmission, e.g. ptosis and yawning, as well as signs of an increased stimulation of dopamine receptors in dopaminoceptive target neurones, e.g. stereotyped sniffing. In contrast, the former signs were exclusively observed after smaller doses and the latter after larger doses of apomorphine. Since it had been shown in previous studies that these signs, except yawning, could be conditioned in association with discriminative stimuli in the environment, the present study using conditioning experiments with this intermediate dose aimed at determining, 1. the time course of each conditioned response, 2. the interaction of conditioned and unconditioned responses, and 3. the conditions under which hypokinesia occurred. In each series, conditioned animals were compared with pseudoconditioned controls. Rats were conditioned for 8 days with apomorphine, and on day 9, treated with saline in presence of the conditional stimuli (a test cage in combination with acoustic and olfactory stimuli). In contrast to pseudoconditioned controls, ptosis and stereotyped behaviour were observed in conditioned rats, sometimes occurring alternatingly. These signs closely resembled the direct, unconditioned pharmacological effects. In addition, akinesia occurred after conditioning, although it was never manifest as a pure drug response, nor during the conditioning period. In contrast, yawning was observed in pseudoconditioned as well as in conditioned rats, although slightly more frequently in the former animals. Subsequently, the rats were again conditioned (or pseudoconditioned) on days 10–14 with apomorphine and both groups tested with the same dose (0.18 mg/kg) of apomorphine in the presence of the conditional stimuli. Both ptosis and stereotypies were significantly enhanced in conditioned animals, indicating synergistic interactions between conditioned and direct, pharmacological behavioural effects. In all cases the conditioned effects lasted for about 30 min. The results show that, after conditioning with an intermediate dose of apomorphine, both signs typical of a low dose of apomorphine and those characteristic of a large dose can be conditioned and sometimes occur alternately.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 343 (1991), S. 559-567 
    ISSN: 1432-1912
    Keywords: Conditioning ; Apomorphine ; EEG ; Stereotyped behaviour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The possible conditioning of pharmacological effects of apomorphine on the electroencephalogram was studied using telemetric recordings in rats. Previous studies have shown that apomorphine-induced stereotyped behaviour can be conditioned: after repeated pairings of defined stimuli with the drug effect, the presentation of the external stimuli alone elicited stereotype sniffing, licking, and gnawing. Since apomorphine, an agonist at dopamine receptors, also produces a characteristic EEG pattern with an increase of power in the alpha-1 band, the possibility that this effect could also be conditioned was studied. In fact, conditioning with a dose of 0.5 mg/kg apomorphine (s. c.) led to a significant increase in the number of short-lasting episodes with enhancement of the power in the alpha-1 range in the presence of the conditioned stimuli, according to a comparison of the results obtained in the conditioned group and those of the controls (“pseudoconditioned”). Moreover, behavioural studies were performed simultaneously in order to find possible correlations between conditioned effects on EEG and conditioned alterations in behaviour. In general, a fair correlation between the increase of power in the alpha-1 band and stereotyped behaviour was found. This was also the case during extinction, when the conditioned stimuli were repeatedly uncoupled from apomorphine administration: both behavioural parameters and EEG alterations showed similar time-courses and had almost disappeared during the fourth extinction session.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 296 (1977), S. 249-254 
    ISSN: 1432-1912
    Keywords: Alpha-motoneurones ; Extensor ; Specific effects of narcotics ; Morphine ; Apomorphine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Specific effects of narcotics (opiates) were studied on rat extensor alpha-motoneurones. The animals were anaesthetized with halothane, artificially ventilated and immobilized with N,N′-diallyl nortoxiferinium-HCl. The alpha-motoneurones were activated by tetanic stimulation of the cut ipsilateral gastrocnemius-soleus (GS) nerve. Morphine (2 and 4 mg/kg) administered intravenously, significantly increased the frequency of reflex discharges. In most of the neurones tested, naloxone (0.25 mg/kg) given intravenously, abolished the effect of morphine. In some neurones, however, naloxone induced a further activation. The dose of naloxone employed was ineffective when given alone. The effect of morphine was mimicked by an intravenous injection of levorphanol (1 mg/kg), but not by an equimolar dose of the stereoisomer dextrorphan, which suggests that the activating effect on alpha-motoneurones is a specific one. An intraperitoneal injection of apomorphine (1 mg/kg) reduced the effect of morphine. The effect of narcotics on alpha-motoneurones parallels narcotic-induced catalepsy and muscular rigidity, with regard to dose-dependence as well as to the antagonism of naloxone and apomorphine, and suggests that both catalepsy and muscular rigidity are mainly due to an activation of extensor alpha-motoneurones. Since this activation can be inhibited by spinalization of the rats, it can be concluded that the activation is due to a supraspinal action of morphine, resulting in a decreased dopaminergic neurotransmission in the brain.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 671-677 
    ISSN: 1432-1912
    Keywords: Apomorphine ; Conditioning ; Stereotypies ; Extinction ; Haloperidol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In previous studies it was established that stereo-typies (sniffing, licking, gnawing) produced by apomorphine can be conditioned and after repeated pairings with defined conditioned stimuli (auditory, tactile + olfactory) these stereotypies can be observed in the presence of the conditioned stimuli alone. In the present experiments, the extinction of these conditioned stereotypies was studied in one series; in another series, the possible inhibition of conditioned stereotypies by the blocker of dopamine receptors, haloperidol, was measured. The rats were conditioned (or the controls pseudoconditioned, respectively) for either 3 or 10 days with 2.0 mg/kg s. c. apomorphine or 6 days with 0.5 mg/kg s. c. of the drug and by placing them into particular cages in the presence of an auditory and an olfactory stimulus. Under all these conditions, episodes of conditioned stereotypies were observed, when solvent + conditioned stimuli instead of apomorphine was applied 1 day after the last conditioning session (first session of extinction). The conditioned responses seemed to be on the highest level after conditioning with 2.0 mg/kg apomorphine 3 days, lower after conditioning with the same dose on 10 days, and even lower after conditioning for 6 days with 0.5 mg/kg. Under all these conditions, the stereotypies summed up and averaged for the total observation period of 60 min rapidly decreased during the extinction period, so that on day 4 of the extinction period, no further significant differences between conditioned and pseudoconditioned animals were observed, although a short initial period was still observed on the fourth day. On day 3 of extinction, not only an early, but also a late episode of conditioned stereotypies was manifest, interrupted by an almost silent period. The acute (unconditioned) stereotypies produced by 0.5 mg/kg s. c. apomorphine were almost completely suppressed by pre-treatment with 0.1 mg/kg i. p. haloperidol. In contrast, the same dose of haloperidol produced a much less pronounced inhibition of conditioned stereotypies after conditioning with the same dose of apomorphine for 6 times. These results, together with previous findings, suggest that the conditioned behavioural effects are not due to an activation of dopaminergic mechanisms during conditioning with apomorphine.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 335 (1987), S. 673-679 
    ISSN: 1432-1912
    Keywords: Apomorphine ; Conditioning ; Dopamine receptors ; Stereotyped behaviour ; Akinesia ptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Interactions between the direct (unconditioned) behavioural effects apomorphine and its conditioned effects after pairing with previously neutral stimuli were studied. Rats were injected once daily for 3–12 times, with apomorphine (2.0 mg/kg or 0.5 mg/kg or 0.07 mg/kg s.c. the dose kept constant in each series), in the presence of defined environmental stimuli (a wire cage in association with an acoustic and an olfactory stimulus) as conditional stimuli. The two larger doses produced stereotyped sniffing, licking, and gnawing, the smallest dose akinesia, ptosis, yawning and penile erections. During the conditioning phase, the drug produced most of the effects with increasing intensity and in the case of the stereotypies, there also was a shift to higher scores of stereotypy, with a reduced latency in onset of the signs. On the test day, 1 day after the last administration of apomorphine, the conditioned rats as well as “pseudoconditioned” controls were treated with a test dose of apomorphine in the presence of the conditional stimuli. Pseudoconditioned rats had been treated with the same pharmacological schedule of apomorphine and had the same familiarity with the stimuli, but both were kept separate. A test dose of 0.5 mg/kg of apomorphine produced stereotypies with a significantly higher score and shorter latency in onset in conditioned than in pseudoconditioned rats. Rats conditioned with the lowest dose showed a significantly longer total duration and a shorter latency in onset of akinesia and ptosis. In rats conditioned with the largest dose (2.0 mg/kg), administration of the lowest dose on the test day produced no stereotypies; neither the akinesia nor the ptosis were different between conditioned and pseudoconditioned rats, but yawning occurred with a higher frequency and a shorter latency in pseudoconditioned rats. When rats were conditioned with the lowest dose and tested with 0.5 mg/kg, the level of stereotypies was identical in both groups of rats, whereas akinesia and ptosis were not observed. Yawning and penile erections occurred more frequently, but for short periods only, in conditioned rats. The results showed that apomorphine-induced stereotypies, akinesia and ptosis could be conditioned, and the conditioned effects mimicked the unconditioned responses, which depended on the dose. Conditioned and unconditioned signs of an increased dopaminergic neurotransmission, observed after large doses of apomorphine, thus acted in a synergistic way; the same applied to conditioned and unconditioned signs observed after a small dose and were perhaps due to a decreased dopaminergic transmission. In contrast, when conditioned and unconditioned signs acted in a mutually antagonistic way (increased vs. decreased dopaminergic transmission), the unconditioned signs predominated.
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  • 6
    ISSN: 1432-2072
    Keywords: Apomorphine ; Conditioned dopaminergic activity ; Stereotyped behaviour ; Dopamine autoreceptors ; Dopamine metabolism ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated whether pharmacological effects of the dopamine agonist apomorphine can be conditioned by establishing an association of apomorphine administration with exteroceptive cues. Apomorphine was repeatedly administered and subsequently, the rat was put into a test cage and exposed to an acoustic and an olfactory stimulus (“conditioned rats”). Control animals (“pseudoconditioned” rats) were treated with the same pharmacological schedule of apomorphine not temporally associated with the stimuli. On the test day, both groups were injected with saline and exposed to the stimuli described. The stereotyped behaviour produced by large doses of apomorphine (0.5 or 2.0 mg/kg SC), namely sniffing, licking and gnawing, could be conditioned in a pronounced way. During the conditioning period, a change in the stereotypies was observed with regard to the time-course (earlier occurrence) and to the character of the stereotypies (from sniffing to licking and gnawing), when 0.5 mg/kg apomorphine was used, but not with the dose of 2.0 mg/kg. The conditioned responses showed a relatively uniform distribution during the observation period with some increase towards the end of the observation period. Some signs produced by a low dose of apomorphine (0.07 mg/kg SC), namely hypomotility and ptosis, but not yawning, could also be conditioned, although in a less pronounced way. An intermediate dose of apomorphine (0.18 mg/kg SC) produced both signs observed after large doses and those observed after a small dose, occurring alternatingly. Both types of signs could be conditioned using this dosage. Conditioning did not alter striatal or mesolimbic dopamine turnover. These results suggest that only behavioural signs due to an activation of postsynaptic dopamine receptors, but also some symptoms produced by an activation of dopamine autoreceptors can be conditioned.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 101 (1990), S. 421-428 
    ISSN: 1432-2072
    Keywords: Conditioning ; Apomorphine ; Locomotor activation ; Stereotyped behaviour ; Glutamate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It was shown previously that behavioural effects of apomorphine (locomotor activation and stereotyped behaviour) can be conditioned when they are associated with well-defined environmental stimuli. In the present study, the hypothesis was tested that glutamatergic mechanisms play an important role either in formation of conditioned responses to apomorphine or in the expression of previously established conditioned responses. For this purpose, two blockers of glutamate receptors were applied, either MK-801 (dizocilpine), a non-competitive, but selective blocker of NMDA-type receptors or MLV-6976, a non-selective blocker of glutamate receptors. MK-801 produced some locomotor activation by itself in a dose-dependent way (0.125–0.50 mg/kg ip). The locomotor activation produced by 0.25 mg/kg could not be conditioned. When rats were conditioned 9 times with 2 mg/kg apomorphine after pretreatment with 0,25 mg/kg of MK-801, this pretreatment did not prevent the development of apomorphine-conditioned locomotor activity or stereotypies which appeared when the rats were treated with saline in presence of the conditioned stimuli. Similar results were obtained when rats were conditioned 7 times with the same dose of apomorphine after pretreatment with 20 mg/kg ip MLV-6976, which drug did not induce any visible alterations in motility by itself. When rats were conditioned 7 times with 2 mg/kg apomorphine alone and tested with MK-801 (0.25 mg/kg) in the presence of the conditioned stimuli, neither locomotor activity nor stereotypies appeared as conditioned responses. When rats were conditioned with the same dose of apomorphine alone and tested with MLV-6976 (20 mg/kg ip), stereotypies did not appear as conditioned responses, but some locomotor activity occurred. The results suggest that glutamatergic mechanisms are not relevant for the development of conditioned responses to apomorphine, but might be of some relevance for the expression of previously established conditioned responses.
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  • 8
    ISSN: 1432-2072
    Keywords: Apomorphine ; Stereotypy ; Environmental influence ; Automatic recording ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The topography of stereotyped behaviour produced by apomorphine in rats was studied by using either a scoring system, based on observation in a wire cage, or by quantification of horizontal and vertical activities, and of the total distances run in an open field, using an automatic recording system. The latter design was combined with a classification of the type of stereotyped behaviour observed during recording. In addition, the reproducibility of the nature of the stereotyped behaviour and its dose-dependence in individual animals was evaluated. In rats observed in a wire cage, apomorphine at lower doses (0.25 or 0.50 mg/kg SC) produced stereotyped sniffing. Increasing the doses led to stereotyped licking and the largest dose (5.00 mg/kg SC) produced predominantly stereotyped gnawing, as was demonstrated graphically. The type of behaviour produced by 2 mg/kg apomorphine in the open field was reproduced well in individuals after a second administration 4 days later. The shift from sniffing to gnawing was observed in most, but not all of the individually classified animals after administration of the largest dose (5 mg/kg). The locomotor part of motility was highest in “sniffing animals” and lower when gnawing occurred. The non-locomotor part of motility was low in “sniffing rats” and increased when licking and gnawing occurred. In some of the animals a characteristic “climbing” behaviour was observed in addition after the larger doses, which did not interfere with sniffing, licking or gnawing. A combination of classification by observation and automatic recording seems the most appropriate way to study the topography of stereotyped behaviour produced by apomorphine.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 42 (1975), S. 225-229 
    ISSN: 1432-2072
    Keywords: Morphine ; Apomorphine ; Dopamine Receptors ; Stereotypies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract These experiments were carried out to investigate whether chronic morphine treatment increases the sensitivity of dopamine receptors in rat brain. This was studied by considering apomorphine effectiveness in a) inducing stereotyped behaviour and b) decreasing the dopamine turnover in the striata. Acute morphine treatment slightly reduced stereotyped behaviour induced by l-Dopa and by apomorphine. In morphine-withdrawn rats, apomorphine was no more effective than saline in inducing stereotypies (sniffing, licking, gnawing). However, the ability of apomorphine to lower striatal dopamine turnover was increased in morphine-withdrawn rats. Despite these latter observations, chronic morphine treatment probably did not induce a supersensitivity of dopamine receptors in rat brain.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 308 (1979), S. 149-154 
    ISSN: 1432-1912
    Keywords: α-Motoneurones ; Haloperidol ; Apomorphine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Effects of haloperidol on rat flexor and extensor α-motoneurones were studied in ventral roots of laminectomized rats under halothane anesthesia. The α-motoneurones were activated by tetanic stimulation of low-threshold afferents (group I and II), either of the ipsilateral peroneal nerve (“flexor α-motoneurones”) or gastrocnemius-soleus nerve (“extensor α-motoneurones”). Haloperidol, given in the doses of 0.075, 0.15 and 0.30 mg/kg i.p. inhibited the reflex activation of flexor α-motoneurones; higher doses seemed to be more effective than lower ones. Apomorphine (2 mg/kg s.c.) partially antagonized the inhibitory action of haloperidol with some latency. Higher doses of haloperidol (0.15–0.60 mg/kg i.p.) also inhibited the reflex activation of extensor α-motoneurones; this inhibitory effect was, at least for a short time, antagonized by apomorphine (2 mg/kg s.c.). The threshold for reflex activation both of flexor and extensor α-motoneurones was raised by haloperidol and lowered by a subsequent administration of apomorphine. Our results suggest that akinesia and catalepsy, induced in rats by haloperidol might be, at least in part, due to a decrease in sensitivity of α-motoneurones to proprioceptive stimuli.
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